In the present study, we describe an expansion of CD16+ cells with a CD3+ TcR gamma/delta+ phenotype, in the presence of normal numbers of "classic" CD3-CD16+ natural killer (NK) cells, in two patients with human immunodeficiency virus (HIV) infection in late stage. The NK activity of the two subjects was substantially higher then that of HIV+ subjects in the same stage of infection. A second evaluation of one of the patients showed levels of NK activity consistent with the clinical stage of HIV infection, concomitant with a remarkable reduction in the percentage of double-positive CD3/TcR gamma/delta cells. The number of CD16+ cells also reached values comparable to those of the control group. In conclusion, we have identified a population of CD3+TcR gamma/delta+CD16+ cells that have the capability to lyse an NK-sensitive target in two patients with unusually high levels of NK activity.